达雷妥尤单抗治疗复发难治性多发性骨髓瘤及对T细胞亚群、炎症因子、肿瘤相关因子的影响

Effects of daratumumab in treating relapsed and refractory multiple myeloma and its impact on T cell subsets, inflammatory factors, and tumor-associated factors

摘要:

目的 探讨达雷妥尤单抗对复发难治性多发性骨髓瘤（RRMM）患者的治疗效果，及其对T细胞亚群、炎症因子、肿瘤相关因子等指标的影响。方法 选取2021年1月—2024年1月在海军第九七一医院、解放军总医院第五医学中心和康复大学青岛中心医院就诊的80例RRMM患者，根据是否应用达雷妥尤单抗分为对照组和试验组，每组40例。对照组接受VRD（硼替佐米、来那度胺和地塞米松）治疗，试验组接受DVD（达雷妥尤单抗、硼替佐米、地塞米松）治疗。对比两组临床疗效、T细胞亚群水平［调节性T淋巴细胞（Treg）、CD3⁺、CD4⁺、CD4⁺/CD8⁺］、炎症因子［转化生长因子-β（TGF-β）、干扰素-γ（IFN-γ）、白细胞介素-6（IL-6）、C反应蛋白（CRP）］、肿瘤相关因子［乳酸脱氢酶（LDH）、凋亡抑制蛋白Survivin、血管内皮生长因子（VEGF）、β₂-微球蛋白（β₂-MG）］、骨髓浆细胞、血红蛋白（Hb）、血清M蛋白、不良反应上的变化。结果 试验组总缓解率高于对照组（P <0.05）。试验组治疗前后Treg、CD3⁺、CD4⁺、CD4⁺/CD8⁺的差值高于对照组（P <0.05）。试验组治疗前后TGF-β、IFN-γ、IL-6、CRP的差值高于对照组（P <0.05）。试验组治疗前后LDH、Survivin、VEGF、β2-MG的差值高于对照组（P <0.05）。试验组治疗前后骨髓浆细胞、Hb、血清M蛋白的差值高于对照组（P <0.05）。两组患者白细胞减少、血小板减少、乏力、神经性头痛、胃肠道反应及周围神经病变比较，差异均无统计学意义（P >0.05）。结论 达雷妥尤单抗联合硼替佐米和地塞米松治疗RRMM能有效改善患者的免疫调节、炎症反应、肿瘤抑制及骨髓功能，同时具有较好的安全性，值得在临床进一步推广应用。

Abstract:

Objective To investigate the therapeutic effects of daratumumab in patients with relapsed and refractory multiple myeloma (RRMM) and its impact on T cell subsets, inflammatory factors, and tumor-associated factors.Methods A total of 80 RRMM patients treated at our hospitals from January 2022 to January 2024 were selected, and they were divided into a control group (n = 40) and an experimental group (n = 40) based on whether they received daratumumab. The control group received VRD (bortezomib, lenalidomide, and dexamethasone) treatment, while the experimental group received DVD (daratumumab, bortezomib, and dexamethasone) treatment. The clinical efficacy, T-cell subsets [frequencies of regulatory T cells (Treg), CD3⁺ T cells and CD4⁺ T cells, and the ratio of CD4⁺/CD8⁺ T cells], inflammatory factors [transforming growth factor-β (TGF-β), interferon-γ (IFN-γ), interleukin-6 (IL-6), and C-reactive protein (CRP)], tumor-associated factors [lactate dehydrogenase (LDH), survivin, vascular endothelial growth factor (VEGF), and β₂-microglobulin (β₂-MG) ], frequency of bone marrow plasma cells, levels of hemoglobin (Hb) and serum M protein, and adverse effects were compared between the groups.Results The overall response rate in the experimental group was higher than that in the control group (P < 0.05). The differences in frequencies of Treg, CD3⁺ T cells and CD4⁺ T cells and the ratio of CD4⁺/CD8⁺ T cells before and after treatment in the experimental group were significantly higher than those in the control group (P < 0.05). The differences in levels of TGF-β, IFN-γ, IL-6, and CRP before and after treatment in the experimental group were greater than those in the control group (P < 0.05). The differences in levels of LDH, survivin, VEGF, and β₂-MG before and after treatment in the experimental group were higher than those in the control group (P < 0.05). The differences in the frequency of bone marrow plasma cells and levels of Hb and serum M protein before and after treatment in the experimental group were higher than those in the control group (P < 0.05). There was no statistically significant difference between the groups in terms of incidence of leukopenia, thrombocytopenia, fatigue, neuropathic headache, gastrointestinal reactions, and peripheral neuropathy (P > 0.05).Conclusions The combination of daratumumab with bortezomib and dexamethasone for treating RRMM effectively improves immune regulation, inflammatory response, tumor suppression, and bone marrow function in patients while maintaining a good safety profile, making it a viable option for further clinical application.